Taxifolin (5,7,31,41-tetrahydroxyflavanol,dihydroquercetin) is a member of the flavonoid family. Moleculars of a similar structure to Taxifolin (such as Quertsetin, Myricetin, Dihydromyricetin, Catechin) elicit a wide range of pharmacological effects of anti-oxidation and anti-radiation [1.2] (see [References] herein below).
Furthermore, all mentioned flavonoids also have anti-inflammation activity, anti-viral activity, anti-tumor activity, and protective postmenopausal osteoporosis activity [3-6]. Due to its pharmacological diversity, its bioavailability and biological properties have raised a great interest for future studies [7-8].
Flavonoids, including Taxifolin, are slightly soluble in water and show a slow dissolution rate from solid oral dosage forms, restricting their clinical use. The poor solubility of active pharmaceutical ingredients in water and their low dissolution rate in the aqueous gastro-intestinal fluids often leads to insufficient bioavailability; which becomes one of the most difficult problems in pharmaceutical and food supplement technology.
The dissolution of poor water-soluble drugs that undergo rate-limited gastrointestinal absorption can generally be improved with many techniques, one of which is the preparation of nanodispersion [8-10]. This technology provides the possibility of reducing the drug particle size. With polyvinylpyrrolidone (PVP) selected as the carrier, this increases the surface area and hence, improves the dissolution rates [11,12].
An alternative way to increase solubility is by using the polyglycol molecules[13] or infusion complexes with Cyclodextrines[14].
The analysis of the data leads to the conclusion that existing methods and approaches for improving solubility in water, or for creating completely water-soluble compositions, have many limitations and do not yet lead to their widespread use in the creation of new effective pharmaceutical preparations or water-soluble food additives.
The use of polyglycols to increase solubility in water or a high concentration of cyclodextrins is in some cases unacceptable for the final product. In addition, instability of the complexes leads to the possibility of crystallization of said insoluble product, just as the use of heating and using solvents in their preparation acts in the same manner.
An attempt to create a water soluble composition was done with a combination of Taxifolin and Rutine with a glycoside group in the structure. That mixture is achieved in solution only by heating to 60 degrees Celsius, and the data of such complex stability is missing.
In patents [16] a water soluble composition was prepared with mixing Taxifolin and L-arginine in an Argon atmosphere, which illustrates the instability of such mixture. Data about stabilization of water solution is also missing. The same drawback is seen in patent [17], that uses a mixture of flavonoids including Taxifolin as a part of Silybum Marianum, a mixture of basic amino acids (including L-arginine), polyols and amorphous Mg/Al metasilicate that helps formulation.
Thus, the use of new approaches for the creation of stable water-soluble bioflavonoids and their subsequent application in the development of new effective pharmaceuticals and food additives is still in high demand.
Examples of such approaches follow ([References]):
1. Sun, X.; Chen, R. C.; Yang, Z. H.; Sun, G. B.; Wang, M.; Ma, X. J.; Yang, L. J.; Sun, X. B. Taxifolin prevents diabetic cardiomyopathy in vivo and in vitro by inhibition of oxidative stress and cell apoptosis. Food Chem. Toxicol. 2013, 63, 221-232. [Cross Ref] [Pub Med].
2. Tiukavkina, N. A.; Rulenko, I. A.; Kolesnik, I. U. A. Dihydroquercetin-anewantioxidantandbiologicallyactive food sdditive. J. Vopr. Pitan. 1997, 6, 12-15.
3. Oi, N.; Chen, H. Y.; Kim, M. O.; Lubet, R. A.; Bode, A. M.; Dong, Z. G. Taxifolin suppresses UV-induced skin carcinogenesis by targeting EGFR and PI3K. Cancer Prey. Res. 2012, 5, 1103-1114. [Cross Ref] [Pub Med]
4. Satue, M.; Arriero, M. M.; Monjo, M.; Ramis, J. M. Quercitrin and taxifolin stimulate osteoblast differentiation in MC3T3-E1cellsandinhibitosteoclastogenesisinRAW264.7cells. Biochem. Pharmacol. 2013, 86, 1476-1486. [Cross Ref] [Pub Med]
5. Tamara, V. A.; Antonina, F. K.; Ludmila, N. K.; Maria, K. L.; Vera, V. S.; Yuri, N. K. Effects of taxifolin on the activity of angiotensin-converting enzyme and reactive oxygen and nitrogen species in the aorta of aging rats and rats treated with the nitric oxide synthase. Age 2013, 35, 2089-2097.
6. Verma, S.; Singh, A.; Mishra, A. Dual inhibition of chaperoning process by taxifolin: Molecular dynamics imulation study. J. Mol. Graph. Model. 2012, 37, 27-38. [Cross Ref] [Pub Med].
7. UHPLC-MS/MS Determination, Pharmacokinetic, and Bioavailability Study of Taxifolin in Rat Plasma after Oral Administration of its Nanodispersion Chun-Juan Yang 1, Zhi-Bin Wang 2,*, Ying-Ying Mi 2, Ming-Jie Gao 1, Jin-Nan Lv 2, Yong-Hai Meng 2, Bing-You Yang 2 and Hai-Xue Kuang 2,* 1 College of Pharmacy, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, Heilongjang, China; chunjuanyang@126.com (C.-J. Y.); gaomingjie8888@163.com (M.-J. G.) 2 Key Laboratory of Chinese Materia Medica (Ministry of Education), Heilongjiang University of Chinese Medicine, Harbin 150040, Heilongjang, China; ccmini731@163.com (Y.-Y. M.); liyufeng5211314@126.com (J.-N. L.); 15845002546@139.com (Y.-H. M.); ybywater@163.com (B.-Y. Y.)*Correspondence: wzbmailbox@126.com (Z.-B. W.); hxkuang@yahoo.com (H.-X. K.); Tel./Fax: +86-451-8726-6862 (Z.-B. W. & H.-X. K.) Academic Editor: Derek J. McPhee Received: 6 Mar. 2016; Accepted: 11 Apr. 2016; Published: 14 Apr. 2016
8. Published in final edited form as: J Neurosci. 2012 Jan. 4; 32(1): 390-401
9. Kallay, N.; Zalac, S. Stability of nanodispersions: A model for kinetics of aggregation of nanoparticles. J. Colloid Interface Sci. 2002, 25, 70-76. [Cross Ref] [Pub Med]
10. Nkansah, P.; Antipas, A.; Lu, Y.; Varma, M.; Rotter, C.; Rago, B.; El-Kattan, A.; Taylor, G.; Rubio, M.; Litchfield, J. Development and evaluation of novel solid nanodispersion system for oral delivery of poorly water-soluble drugs. J. Control. Release 2013, 169, 150-161. [Cross Ref] [Pub Med]
11. Tam, J. M.; Mcconville, J. T.; Williams, R. O., III; Johnston, K. P. Amorphous cyclosporin nanodispersions for enhanced pulmonary deposition and dissolution. J. Pharm. Sci. 2008, 97, 4915-4933. [Pub Med]
12. Constantinides, P. P.; Chaubal, M. V.; Shorr, R. Advances in lipid nanodispersions for parenteral drugdelivery and targeting. Adv. Drug. Deliv. Rev. 2008, 60, 757-767. [Cross Ref] [Pub Med]
13. Shikov, A. N.; Pozharitskaya, O. N.; Sabiruddin Mirza, I. M.; Urakovalrina, N.; Hirsjarvi, S.; Makarov, V. G.; Heinamaki, J.; Yliruusi, J.; Hiltunenc, R. Nanodispersions of taxifolin: Impact of solid-state propertieson dissolution behavior. Int. J. Pharm. 2009, 377, 148-152. [Cross Ref] [Pub Med]
14. Formulation of microencapsulated food ingredients for fat containing products. Patentpak by
Bazarova Yu. G, Moskalev E. V, Andreeva N. Yu; Bazarova A. V. From Russ. (2009). Language:Russian, Database CAPLUS
15. Asian Journal of Pharmaceutical sciences 9(2014) 304-3166
16. Water soluble flavonoid composition, and foods, beverages, and cosmetics containing them. Patentpak. By Hashizume, Yujiz Takado, Taketoshi; Iida, Junji From Jpn. Kokai Tokkyo Koho (2008), JP 2008092869 A Apr. 24, 2008/Language: Japanese, Database: CAPSUL
17. Water soluble pharmaceutical composition L-arginine-Dihydroqurcetin and method of obtaining thereof. Patentpak.
By Koroteev A. M; Kaziev G. Z., Koroteev M. P., Zinchenko V. P, Teleshev A. T., Perepelkin M. V. From Russ. (2015), RU 2545905 C1 Apr. 10, 2015/language: Russian, Database: CAPLUS
18. Water-soluble formulation based on flavanol lignans and process for their preparation.
PATENTPAK By Stuchlik, Milan; Kopenec, Jiri From Czech Rep. (2009), CZ 300846 B6 Aug. 26, 2009./language: Czech, Database: CAPLUS